Characterization of Antioxidant and Antimicrobial Activity and Phenolic Compound Profile of Extracts from Seeds of Different Vitis Species.

Seeds of Vitis vinifera L. with a high content of bioactive compounds are valuable by-products from grape processing. However, little is known about the bioactivity of seeds from other Vitis species. The aim of this study has been to compare the phenolic composition, antimicrobial activity, and antioxidant activity of extracts from seeds of four Vitis species (V. riparia Michx., V. californica Benth., V. amurensis Rupr., and V. vinifera L.). Antioxidant activities were assessed as ferric-reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) scavenging activity, and oxygen radical absorbance capacity (ORAC). The antimicrobial activity was determined using the microdilution method against some Gram-negative (Escherichia coli, Salmonella enterica ser. Typhimurium, and Enterobacter aerogenes) and Gram-positive (Enterococcus faecalis and Staphylococcus aureus) bacteria. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to evaluate the phenolic profile of extracts. Flavan-3-ols, procyanidins, phenolic acids, flavonols, anthocyanins, and stilbenoids were detected. (+)-Catechin and (-)-epicatechin turned out to be the most abundant in the phenolic profile of V. amurensis seed extract. Phenolic acids prevailed in the extract from V. vinifera seeds. The V. riparia and V. californica seed extracts had higher contents of most individual phenolics compared to the other Vitis species. They also showed a higher total phenolic content, DPPH• scavenging activity, ORAC, and overall antibacterial activity. Total phenolic content significantly correlated with antioxidant activity and antimicrobial activity against E. coli. The principal component analysis (PCA) showed discrimination between V. vinifera, V. amurensis, and clustered V. riparia and V. californica with respect to variables. To recapitulate, this research demonstrates that seeds of different Vitis species, especially V. riparia and V. californica, are sources of molecules with antioxidant and antimicrobial activities that can be used in different sectors, such as in the food, cosmetic, and pharmaceutical industries.

Nutraceutical Potential of Leaf Hydro-Ethanolic Extract of the Edible Halophyte Crithmum maritimum L.

Aromatic halophytes represent an exceptional source of natural bioactive compounds for the food industry. Crithmum maritimum L., also known as sea fennel, is a halophyte plant colonizing cliffs and coastal dunes along Mediterranean and Atlantic coasts. It is well known to produce essential oils and polyphenols endowed with antioxidant and biological effects. The present work reports the phytochemical profile, as well as antioxidant, antimicrobial and antimutagenic properties of C. maritimum leaf hydro-alcoholic extract. From LC-ESI-MS analysis, eighteen phenolic compounds were depicted in sea fennel extract and the amount of total phenolic content exceeds 3% DW. Accordingly, C. maritimum extract showed strong antioxidant activities, as evidenced by in vitro (DPPH, ORAC, FRAP) and ex vivo (CAA-RBC and hemolysis) assays. An important antimicrobial activity against pathogenic strains was found as well as a strong capacity to inhibit Staphylococcus aureus (ATCC 35556) biofilm formation. Sea fennel extracts showed a significant decrease of mutagenesis induced by hydrogen peroxide (H2O2) and menadione (ME) in Saccharomyces cerevisiae D7 strain. In conclusion, our results show that C. maritimum is an exceptional source of bioactive components and exert beneficial effects against oxidative or mutagenic mechanisms, and pathogenic bacteria, making it a potential functional food.

The combined effect of Sango sprout juice and caloric restriction on metabolic disorders and gut microbiota composition in an obesity model.

The main purpose of this study was to compare the benefits of SSJ supplementation in obese rats with those achieved only by switching the alimentary regimen from high-fat (HFD) to the regular one (RD) in liver, ileum and prostate. Furthermore, changings in caecal chime microbiota were investigated. SSJ was administered to rats in combination with a RD (HFD-RD + SSJ). The switch from HFD to RD led to a weight loss of almost 9.8 g, and the total cholesterol was found to be significantly lower. In the HFD-RD + SSJ group, all values were improved compared with the HFD control, and the weight decrement was higher (-23.29 g) with respect to HFD-RD. HFD led to a widespread increment of oxidative stress (OS) markers in liver, ileum and prostate. SSJ has shown to improve the results achieved by the suspension of HFD and it has proven effective wherever the only switch in diet regimen failed.

Effect of farming system on donkey milk composition.

BACKGROUND: Donkey milk is considered as a functional food for sensitive consumers, such as children who are allergic to cow milk. No information is available regarding the effect of farming systems on the quality of donkey milk. The present study aimed to evaluate the effect of the farming system and lactation stage on donkey milk with respect to gross composition, as well as fat-soluble vitamins and fatty acids (FA). RESULTS: Individual milk samples were collected from lactating jennies (n = 53) on the six of the largest farms located in North West Italy. The performance of lactating jennies, herd characteristics and feeding strategies were recorded at each milk sampling. The gross composition of the milk, along with the fat-soluble vitamin content, differed in accordance with the farming system. The lactation stage had limited effects on milk quality. A higher milk fat content corresponded to a higher amount of fresh herbage proportion in the diet, with the highest polyunsaturated fatty acid (PUFA), C18:1c9, C18:3n-3, n-3 FA, retinol and α-tocopherol content and the lowest concentrations of the FA that are less favorable for human health in the milk of animals fed on only forage diets. CONCLUSION: Extensive farming of dairy donkeys increased the fat content and fat-soluble vitamin concentration of milk and also altered the FA composition to a more favorable profile for human nutrition. © 2017 Society of Chemical Industry.

Effects of dietary alfalfa flavonoids on the performance, meat quality and lipid oxidation of growing rabbits.

OBJECTIVE: The present experiment has tested the effect of dietary alfalfa flavonoids (AAF) supplementation on the productive performances, carcass characteristics, meat quality and lipid oxidation of growing rabbits. METHODS: One hundred and sixty crossbred rabbits (42 days old) were divided into four groups of forty animals each and were fed either a control diet (AAF0) or an AAF0 diet supplemented with 400, 800, or 1,200 mg of AAF/kg per diet (AAF4, AAF8, and AAF12, respectively) from weaning to slaughtering (102 days old). Performance data were recorded over a period of 60 days. At the end of the trial, 12 rabbits were slaughtered per group, and the carcass characteristics were recorded. Moreover, the plasma, liver and dorsal muscles were sampled from 12 rabbits/group, and were analyzed for lipid oxidation. RESULTS: No significant differences were recorded for the performance, carcass characteristics and meat quality traits except for lightness parameter that was lower in the control group. Dietary AAF supplementation significantly (p<0.01) affected the malondialdehyde (MDA) levels of the frozen meat in a dose-related manner, with the lowest value (0.24 mg MDA/kg fresh meat) recorded in the AAF12 group samples. CONCLUSION: These findings indicated that the dietary inclusion of AAF in rabbit diets improved muscle oxidation stability with no adverse effects on the growth performance of the animals even if a slight impact on meat lightness color parameter was recorded.

Effect of white wheat bread and white wheat bread added with bioactive compounds on hypercholesterolemic and steatotic mice fed a high-fat diet.

BACKGROUND: The effects of white wheat bread and white wheat bread added with a bioactive compound mixture (Cyclanthera pedata, Glycine max, Monascus-fermented red mold rice, Cynara scolymus and Medicago sativa) were examined on hypercholesterolemic and steatotic mice, divided into four groups: control diet (CTR), high-fat diet (HFD), high-fat diet with white wheat bread added with 1.5 g kg(-1) of mixture (HFD+AB) and high-fat diet with white wheat bread (HFD+B). RESULTS: Total serum cholesterol in the HFD+AB and HFD+B groups and hepatic triglycerides in the HFD+AB group decreased compared with the HFD group. Liver histology confirmed lower lipid drop accumulation in the HFD+AB group than in the HFD and HFD+B groups. HFD+AB caused a 7.0-fold increase and a 3.5-fold reduction in CYP7A1 and SREBP-1c gene expression respectively compared with the HFD group. Moreover, the HFD+B group showed a 2.2-, 8.4- and 1.5-fold increase in HMG CoA reductase, CYP7A1 and LDLr gene expression respectively compared with the HFD group. CONCLUSION: Both the white wheat bread and the added white wheat bread induced cholesterol reduction by increasing CYP7A1. Moreover, the added white wheat bread improved steatosis by decreasing SREBP-1c gene expression.

Probing the alterations in mice cecal content due to high-fat diet.

The global prevalence of obesity more than doubled between 1990 and 2022. By 2022, 2.5 billion adults aged 18 and older were overweight, with over 890 million of them living with obesity. The urgent need for understanding the impact of high-fat diet, together with the demanding of analytical methods with low energy/chemicals consumption, can be fulfilled by rapid, high-throughput spectroscopic techniques. To understand the impact of high-fat diet on the metabolic signatures of mouse cecal contents, we characterized metabolite variations in two diet-groups (standard vs high-fat diet) using FTIR spectroscopy and multivariate analysis. Their cecal content showed distinct spectral features corresponding to high- and low-molecular-weight metabolites. Further quantification of 13 low-molecular-weight metabolites using liquid chromatography showed significant reduction in the production of short chain fatty acids and amino acids associated with high-fat diet samples. These findings demonstrated the potential of spectroscopy to follow changes in gut metabolites.

Assessment of the Antioxidant and Hypolipidemic Properties of Salicornia europaea for the Prevention of TAFLD in Rats.

Halophyte species represent valuable reservoirs of natural antioxidants, and, among these, Salicornia europaea stands out as a promising edible plant. In this study, young and old S. europaea leaves were compared for the content of bioactive compounds and antioxidant activity to assess changes in different growth phases; then, the potential protective effects against low-dose CCl4-induced toxicant-associated fatty liver disease (TAFLD) were investigated by administering an aqueous suspension of young leaves to rats daily for two weeks. Quantification of total and individual phenolic compounds and in vitro antioxidant activity assays (DPPH, FRAP, and ORAC) showed the highest values in young leaves compared to mature ones. Salicornia treatment mitigated CCl4-induced hepatic oxidative stress, reducing lipid peroxidation and protein carbonyl levels, and preserving the decrease in glutathione levels. Electronic paramagnetic resonance (EPR) spectroscopy confirmed these results in the liver and evidenced free radicals increase prevention in the brain. Salicornia treatment also attenuated enzymatic disruptions in the liver's drug metabolizing system and Nrf2-dependent antioxidant enzymes. Furthermore, histopathological examination revealed reduced hepatic lipid accumulation and inflammation. Overall, this study highlights Salicornia's potential as a source of bioactive compounds with effective hepatoprotective properties capable to prevent TAFLD.

Chlamydomonas agloeformis from the Ecuadorian Highlands: Nutrients and Bioactive Compounds Profiling and In Vitro Antioxidant Activity.

Green microalgae are single-celled eukaryotic organisms that, in recent years, are becoming increasingly important in the nutraceutical, cosmetic, and pharmaceutical fields because of their high content of bioactive compounds. In this study, a particular green microalga was isolated from freshwater highland lakes of Ecuador and morphologically and molecularly identified as Chlamydomonas agloeformis (ChA), and it was studied for nutritional and nutraceutical properties. The phenolic composition and the fatty acids profile of lyophilized cells were determined. The methanolic extract was analyzed for the phenolic compounds profile and the antioxidant capacity by means of in vitro tests. Finally, Human Microvascular Endothelial Cells (HMEC-1) were exploited to explore the capacity of ChA to reduce the endothelial damage induced by oxidized LDL-mediated oxidative stress. The extract showed a good antioxidant ability thanks to the high content in polyphenolic compounds. The observed decrease in HMEC-1 cells endothelial damage also was probably due to the antioxidant compounds present in the extract. Based on the outcomes of our in vitro assays, ChA demonstrated to be a promising source of bioactive compounds possessing exceptional antioxidant capacities which make it a prospective functional food.

Characterization and stability evaluation of Egyptian propolis extract nano-capsules and their application.

The increasing demand for natural products and biotechnological activities from bees facilitate their widespread use in food preservation and beneficial effects on humans. This study aimed to prepare and characterize the nano-capsules of Qaluiobia (PQG) governorates propolis extracted with water, ethanol and supercritical fluid-carbon dioxide at 50 °C with co-solvent. Propolis bioavailability was analyzed and introduced to prepare crackers to extend their shelf life. Nano-encapsulation was examined using transmission electron microscopy (TEM), differential scanning calorimetry (DSC) and antioxidant activity. Ethanol and supercritical fluid-carbon dioxide (SCF-CO2) at 50 °C with ethanol as co-solvent recorded higher yield, antioxidant activities, total phenolics and total flavonoids. SCF-CO2 extracts had a higher flavonoid concentration. It was revealed that propolis nano-capsules had high-temperature stability and cytotoxic effects against the three tested human cancer cell lines (i.e. PC3, MCF7 and HePG2). The higher overall acceptability of crackers fortified with PQG was achieved with SCF-CO2 at 50 °C and ethanol extract nano-capsules, i.e. 86.57% and 86.29% respectively. The higher ability to retain antioxidant activity reduces the increase of peroxide value (PV), preventing rancidity and increasing the shelf life of crackers during the storage period. Practical application: This study can provide a suitable method for extracting bioactive compounds from propolis, and improve the biological properties and activities by nano-encapsulation, also reveals the extent of its use as a natural antioxidant and anticancer and its application in bakery products as a functional food.

In Vitro Characterization of Antioxidant, Antibacterial and Antimutagenic Activities of the Green Microalga Ettlia pseudoalveolaris.

Recently, green microalgae have gained importance due to their nutritional and bioactive compounds, which makes them some of the most promising and innovative functional foods. The aim of this study was to evaluate the chemical profile and the in vitro antioxidant, antimicrobial and antimutagenic activity of an aqueous extract of the green microalga Ettlia pseudoalveolaris, obtained from the freshwater lakes of the Ecuadorian Highlands. Human microvascular endothelial cells (HMEC-1) were used to determine the ability of the microalga to reduce the endothelial damage caused by hydrogen peroxide-induced oxidative stress. Furthermore, the eukaryotic system Saccharomyces cerevisiae was used to evaluate the possible cytotoxic, mutagenic and antimutagenic effect of E. pseudoalveolaris. The extract showed a notable antioxidant capacity and a moderate antibacterial activity mostly due to the high content in polyphenolic compounds. It is likely that the antioxidant compounds present in the extract were also responsible for the observed reduction in endothelial damage of HMEC-1 cells. An antimutagenic effect through a direct antioxidant mechanism was also found. Based on the results of in vitro assays, E. pseudoalveolaris proved to be a good source of bioactive compounds and antioxidant, antibacterial and antimutagenic capacities making it a potential functional food.

The hypolipidemic, anti-inflammatory and antioxidant effect of Kavolì® aqueous extract, a mixture of Brassica oleracea leaves, in a rat model of NAFLD.

Herein we characterized the bioactive metabolites of the aqueous extract of Kavolì®, a commercial product composed of a mixture of Brassica oleracea leaves, and assessed its potential ameliorating effects in a rat model of non-alcoholic fatty liver disease (NAFLD). Kavolì® extract showed high levels of bioactive compounds and strong in vitro antioxidant activities. Chlorogenic and neochlorogenic acids were identified as the most representative polyphenols. The administration of brassica extract to steatotic rats significantly ameliorated the levels of blood lipids and transaminases, and lipid content and inflammatory markers in liver. Oxidative stress parameters were significantly improved in both liver and brain of steatotic rats. Moreover, plasma and feces levels of short chain fatty acids (SCFAs) were bring back close to control values by Kavolì® treatment, in spite of high fat diet/streptozotocin (HFD/STZ)-induced alterations. The efficacy of Kavolì® in treating hypercholesterolemia, reducing the level of inflammation and cardiovascular disease biomarkers, steatosis and oxidative stress parameters, as well as the ability in modulating SCFAs levels is probably related to the bioactive compounds of the water extract administered to the rat model of NAFLD. In particular, the ameliorating effects are largely attributable to the high content in polyphenols observed in our study.

Gelatin-based coating enriched with blueberry juice preserves the nutraceutical quality and reduces the microbial contamination of tomato fruit.

To preserve quality and extend the shelf life of tomato, a bioactive edible coating was prepared using gelatin wastes from pharmaceutical industry and lyophilised blueberry juice (BJ). The effectiveness of gelatin-coating (G) and G enriched with blueberry juice (GB) was tested, monitoring carotenoids, polyphenols and flavonoids content, the antioxidant activity and the antimicrobial efficiency of coating against the native microflora.After 7 d of storage, coated fruit showed higher phenolic and flavonoids content and increased antioxidant activity, while carotenoids were unaffected by the treatments. The growth of mesophilic bacteria of GB, and the growth of coliform bacteria of G and GB were significantly reduced during the entire period. The results indicate that GB preserved the nutritional quality of tomatoes and that BJ was able to increase the antimicrobial activity of the coating. This paves the way for a possible use of this biodegradable waste polymer as an eco-friendly coating material.

Effects of fetal number on acute phase proteins, cortisol, and hematological parameters in ewes during the periparturient period.

Many subclinical diseases associated with inflammation occur in sheep during the periparturient period. Clinical symptoms are usually detected at an advanced stage of the disease; therefore, there are considerable risks of permanent health disorders in fetuses or dams. Determination of acute phase proteins (APPs) as markers of inflammation may allow for an earlier diagnosis and effective treatment. Furthermore, multi-fetus pregnancies are often associated with hematological disturbances. The study objective was to compare plasma concentrations of serum amyloid A (SAA), haptoglobin (Hp), fibrinogen (Fb), and cortisol in ewes bearing one and two fetuses in the period from 2 weeks before to 2 weeks after parturition as well as to determine hematological parameters in peripheral blood. There was an important effect of fetal number on APP and cortisol concentrations in periparturient ewes. There was a greater concentration of SAA, Hp, Fb, and cortisol in ewes bearing two fetuses compared with those bearing one fetus. Profiles for APP and cortisol concentrations and hematological parameters were similar for ewes bearing one and two fetuses, and trends were within normal reference ranges for the periparturient period. Furthermore, there were no differences in values for hematological variables between ewes bearing one and two fetuses. with there being no ewes with anemia. In summary, separate determination of the previously undefined physiological ranges of APPs and cortisol for ewes bearing one and two fetuses may facilitate diagnosis of subclinical disorders and enable comparison of laboratory test results with different reference values for ewes bearing different numbers of fetuses.

A survey of ochratoxin A contamination in feeds and sera from organic and standard swine farms in northwest Italy.

BACKGROUND: A survey was carried out on conventional (n = 11) and organic (n = 4) swine farms in northwest Italy in order to investigate the occurrence of ochratoxin A (OTA) in feed and serum samples collected from September 2006 to March 2009. Each farm was sampled twice and a total of 30 feed samples and 285 serum samples were collected. OTA levels were determined through extraction, immunoaffinity column purification and high-performance liquid chromatography analysis coupled with fluorimetric detection. RESULTS: All feed samples resulted to be contaminated with OTA at levels ranging from 0.22 to 38.4 microg kg(-1). The OTA concentrations found in organic feed samples were significantly higher (P < 0.05) than those found in conventional feed samples. All serum samples resulted to be contaminated with OTA at levels ranging from 0.03 to 6.24 ng mL(-1). The OTA concentrations found in organic serum samples were significantly higher (P < 0.001) than those found in conventional serum samples. CONCLUSION: None of the feed samples contained more than the maximum level (50 microg OTA kg(-1), considering a feed moisture content of 120 g kg(-1)) recommended by the European Commission for OTA in complementary and complete swine feedstuffs. The OTA contamination of organic feed and serum samples was found to be significantly higher than that of conventional feed and serum samples.

Polyphenolic characterisation of plant mixture (Lisosan® Reduction) and its hypocholesterolaemic effect in high fat diet-fed mice.

Lisosan® Reduction is a plant mixture produced from powder of fermented Triticum aestivum (Lisosan® G), Desmodium adscendens, Malus domestica, Picrorhiza kurroa and Hordeum vulgare. The aim of this study was to characterise the phenolic profile of Lisosan® Reduction and to evaluate the effects of aqueous extract on mice fed a high fat diet (HFD). Syringic acid, trans sinapic acid and neochlorogenic acid were identified by HPLC-DAD to be the dominant polyphenols of Lisosan® Reduction, followed by vitexin, trans p-coumeric acid and trans ferulic acid. Mice treated with aqueous extract of Lisosan® Reduction (60 mg/kg b.w.) showed a significant decrease of serum cholesterol, glucose and triglycerides level and a significant increase of CYP7A1 gene expression, compared to HFD group.

Comparison of Oxidative Status of Human Milk, Human Milk Fortifiers and Preterm Infant Formulas.

Preterm and low birth weight infants require specific nutrition to overcome the accumulated growth deficit, and to prevent morbidities related to postnatal growth failure. In order to guarantee an adequate nutrient-intake, mother's own milk, when available, or donor human milk, are usually fortified with additional nutrients, in particular proteins. Fortification with processed ingredients may result in additional intake in oxidative compounds, deriving from extensive heat treatments, that are applied during processing. The aim of the present work was to compare the in vitro antioxidant activity and oxidative compound content conveyed by different preterm infant foods and fortifiers, namely raw and pasteurized human milk, two different preterm infant formulas, three bovine milk-based fortifiers and two experimental donkey milk-based fortifiers. Univariate and multivariate statistical analyses revealed significant differences between the different products. The use of human milk minimizes the intake of dietary oxidative compound in comparison to infant formulas, irrespective of pasteurization or fortification, especially as far as malondialdehyde content is concerned. The addition of fortifiers to human milk increases its antioxidant capacity, and the choice of the protein source (hydrolysed vs. whole proteins) differently impacted the resulting total antioxidant capacity of the diet.

Wild Italian Prunus spinosa L. Fruit Exerts In Vitro Antimicrobial Activity and Protects Against In Vitro and In Vivo Oxidative Stress.

Polyphenol-rich foods could have a pivotal function in the prevention of oxidative stress-based pathologies and antibacterial action. The purpose of this study was to investigate the in vitro antimicrobial activity, as well as the in vitro and in vivo antioxidant capacities of wild Prunus spinosa L. fruit (PSF) from the southeast regions of Italy. The total phenolic content (TPC) was quantified, and the single polyphenols were analyzed by HPLC-DAD, showing high rutin and 4-hydroxybenzoic acid levels, followed by gallic and trans-sinapic acids. PSF extract demonstrated antimicrobial activity against some potentially pathogenic Gram-negative and Gram-positive bacteria. Besides, we investigated the cellular antioxidant activity (CAA) and the hemolysis inhibition of PSF extract on human erythrocytes, evidencing both a good antioxidant power and a marked hemolysis inhibition. Furthermore, an in vivo experiment with oxidative stress-induced rats treated with a high-fat diet (HFD) and a low dose of streptozotocin (STZ) demonstrated that PSF has a dose-dependent antioxidant capacity both in liver and in brain. In conclusion, the wild Italian Prunus spinosa L. fruit could be considered a potentially useful material for both nutraceutical and food industries because of its antioxidant and antimicrobial effects.

Dexamethasone counteracts hepatic inflammation and oxidative stress in cholestatic rats via CAR activation.

Glucocorticoids (GCs) are currently used for the therapeutic management of cholestatic diseases, but their use and molecular mechanism remain controversial. The aims of this study were 1) to assess the therapeutic effect of a 2-week treatment with the GC dexamethasone on hepatic damage in bile duct-ligated rats; 2) to investigate its effect on the activation of the nuclear receptors (NRs) pregnane X receptor (PXR), constitutive androstane receptor (CAR) and GC receptor (GR), and NF-kB, as well as on oxidative stress and bile acid (BA) hepatic composition. Cholestasis was induced by ligation of bile duct (BDL animals) in 16 male Wistar-Kyoto rats, and eight of them were daily treated by oral gavage with 0.125 mg/ml/kg DEX for 14 days. Eight Sham-operated rats were used as controls. Severity of cholestasis was assessed histologically and on plasma biochemical parameters. The nuclear expression of NF-kB (p65), GR, PXR and CAR was measured in hepatic tissue by Western Blot. Oxidative stress was evaluated by measuring malondialdehyde, carbonylated proteins, GHS and ROS content in rat livers. LC-MS was used to measure the plasma and liver concentration of 7 BAs. Histological findings and a significant drop in several markers of inflammation (p65 nuclear translocation, mRNA expressions of TNF-α, IL-1ß, IL-6) showed that DEX treatment reversed cholestasis-induced inflammation, and similar results have been obtained with oxidative stress markers. The nuclear expression of p65 and CAR were inversely correlated, with the latter increasing significantly after DEX treatment (p<0.01 vs vehicle). Hepatic BA levels tended to drop in the untreated cholestatic rats, whereas they were similar to those of healthy rats in DEX-treated animals. Plasma BAs decreased significantly in DEX-treated animals with respect to untreated cholestatic rats. In conclusion, DEX reduces inflammation and oxidative stress in BDL rats, and probably CAR is responsible for this effect. Therefore, this NR represents a promising pharmacological target for managing cholestatic and inflammatory liver diseases.

Effect of HFD/STZ on expression of genes involved in lipid, cholesterol and glucose metabolism in rats.

AIMS: The aim of the study was to evaluate lipid, cholesterol and glucose metabolism in a novel rat model of non-alcoholic fatty liver disease (NAFLD). MAIN METHODS: Rats (Wistar) were fed high fat/cholesterol diet (HFD) and a single low dose (35mg/kg) of streptozotocin (STZ). Collagen and glycogen content, oxidative stress and glucokinase activity were measured using biochemical assays. Other metabolic pathways were assessed by qRT-PCR. KEY FINDINGS: HFD/STZ treated rats, compared to control ones, showed an increase in expression of biomarkers of inflammation (TNFα, IL6), fibrosis (TGFß), mitochondrial stress (UCP2) and oxidative stress (GSH and carbonylated proteins) but not of ER stress (CHOP, XBP1). Additionally, HFD/STZ treatment caused a reduction in glycogen content, glucokinase activity (a limiting step in glycolysis) and expression of ChREBP gene (a de novo lipogenesis regulator), suggesting a modified glycolytic pathway. The cholesterol biosynthesis in HFD/STZ treated rats was inhibited (reduced expression of SREBP-2-regulated HMGCoA red and LDLr), instead the cholesterol catabolism was increased, as shown by the mRNA induction of the CYP7A1 and CYP8B1 (key genes for BA acid). A reduced gene expression of FXR-dependent SHP (a key gene for feedback inhibition of CYP7A1 and CYP8B1) and of bile acids (NTCP, OATP1A1, BSEP) and cholesterol (ABCA1) transporters was found. SIGNIFICANCE: These results widely extend the characterization of HFD/STZ rat model, which might mimic the NAFLD/NASH in diabetic humans.